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MODELS TO AID IN PLANNING CANCER SCREENING PROGRAMS
Published in Richard G. Cornell, Statistical Methods for Cancer Studies, 2020
Michael Shwartz, Alonzo L. Plough
If P(C) = .2, P(С IA) = .53. Thus, at a minimum, a chemical that is positive on the Ames test has slightly over a 50% chance of being an animal carcinogen. Since this value is less than 70%, if the Ames test is the only adequate validated test, a positive result does not provide strong enough indication of carcinogenicity to limit worker exposure while awaiting the results of animal bioassay.
Drug Safety Evaluation and Implications for Clinical Investigation
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
The Ames test is sometimes done early because it is a mutagen test, and a large series of known carcinogenic compounds have given positive mutagenic signs in this test. Those wishing to determine early in the development of a compound whether they may face extensive mutagenicity testing later on can conduct this test to exclude those chemicals that are mutagenic to certain special strains of Salmonella typhimurium. A negative response in this test does not necessarily mean that the compound will be free of mutagenic or carcinogenic effect in other in vitro or in vivo tests.
Penicillium and Talaromyces
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Elena Bermúdez, Félix Núñez, Josué Delgado, Miguel A. Asensio
The Ames test is a classic assay used to assess the mutagenic potential of molds or its metabolites that produce genetic damage leading to gene mutations.68 The test uses a number of histidine-auxotrophic Salmonella typhimurium strains carrying different point mutations in genes of the histidine operon. These mutations can revert to wild type when a mutagen is present. Many strains of Penicillium or their mycotoxins led to negative results in Ames test, even when rat liver S9 mix was used as an external metabolizing enzyme system or when a preincubation of toxins in cultured rat hepatocytes was performed. This enzyme treatment is necessary for some compounds to be mutagenic because they need a metabolic liver transformation that bacterial systems do not possess. Ochratoxin A showed no evidence of mutagenic activity by SOS spot and Ames tests,61 in contrast to the results obtained with more sensitive bioassays, such as cell cultures or experimental animals, as discussed later.
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
A wide variety of reliable short-time (rapid) genotoxicity and mutagenicity tests have been developed to detect direct or indirect mutagenesis (Topaktas and Rencuzogullari 2010, Alkan and Anlas 2015). Wedebye et al. (2015) reviewed all genotoxicity, mutagenicity, carcinogenicity, and teratogenicity tests in their study. Methods that are known today as rapid genotoxicity tests and used to determine whether a chemical substance is genotoxic, are Sister Chromatid Exchange (SCE) (Tucker et al. 1993), Chromosome aberration (CA) (Anderson 1988, Carrano and Natarajan 1988, Hagmar et al. 1994), and micronucleus (MN) (Heddle et al. 1991, Fenech 2000). These tests can be applied as in vitro to human peripheral lymphocytes or in Chinese Hamster Ovary (CHO) cells and as in vivo to bone marrow cells of experimental animals such as rats and mice. Another test, known as the Ames test, is one of the most reliable tests that is used to detect the mutagenic effects of chemicals on nucleotide exchange by using Salmonella typhimurium mutant strains (Maron and Ames 1983). In addition, some tests are performed to detect Unscheduled DNA synthesis (UDS) in various cells of living things. The UDS assay is a test used to measure the ability of cells’ nucleotide excision repair system. Tests that are applied in mouse lymphoma cells to detect nucleotide changes also provide useful information about the mutagenic effects of chemicals.
Aloe vera and artemisia vulgaris hydrogels: exploring the toxic effects of structural transformation of the biocompatible materials
Published in Drug Development and Industrial Pharmacy, 2021
Taskeen Frasat, Ume Ruqia Tulain, Alia Erum, Uzma Saleem, Muhammad Farhan Sohail, Rizwana Kausar
Mutagenicity is one of the major adverse effects of any chemical that hinders its potential of becoming a marketable drug. Toxic effects of any chemical can be due to certain chemical structures or substructures called toxicophores [36]. The Ames test is the most widely used initial screening test to determine the mutagenic potential of new chemicals, excipients, and drugs. The test is based on the understanding that a substance that is mutagenic in bacteria (Salmonella typhimurium) might be subsequently carcinogenic in animals and humans. These salmonella strains have one mutant gene that restricts them from producing histidine using bacterial cultural media thus; they can only survive in histidine-rich media. However, if the presence of mutagenic substance results in reversion i.e. conversion of the mutant gene to normal gene allowing bacteria to grow in normal media [37]. Mutagenic testing of both hydrogels was done and results were calculated in terms of positive wells that demonstrated mutagenicity (production of revertant salmonella colonies) (Table 1). This assay was performed using liquid culture and scored by counting the number of negative and positive wells that turned yellow from purple in a 96 well microplate. Two types of Salmonella strains i.e. TA-98 and TA-100 were used in the study. The Salmonella TA-98 strains detect frameshift mutation and the number of positive wells for Aloe vera and Artemisia vulgaris was 13 and 20 respectively. The Salmonella TA-100 strain detects base-pair substitution and it was scored as 13 and 18 for Aloe vera and Artemisia vulgaris respectively. Hence both the test substances appeared to be non-mutagenic [38].
Purified and specific cytoplasmic pollen extract: a non-hormonal alternative for the treatment of menopausal symptoms
Published in Gynecological Endocrinology, 2020
Andrea Genazzani, Nick Panay, Tommaso Simoncini, Herman Depypere, Alfred Mueck, Christian Egarter, Nicoletta Biglia, Tomas Fait, Martin Birkhaeuser, Sven O. Skouby, Mark Brincat, Steven Goldstein, Xiangyan Ruan, Cuauhtémoc Celis-Gonzales, Santiago Palacios
An OECD-approved genotoxicity test (the Ames test) has also been performed with PureCyTonin® to determine potential mutagenic activity. The Ames test uses bacteria to test whether a given product can cause mutations in the DNA of the test organism. It therefore serves as a quick and convenient assay to estimate the carcinogenic potential of a compound. The potential of PureCyTonin® for inducing reverse gene mutations has been examined, although no mutagenic activity was observed when the product was assessed using the Ames test [14,15]. A non-mutagenic extract is generally considered to have no carcinogenic potency and does not need to be further investigated for carcinogenesis.